MEDyC Unit CNRS UMR n° 7369, Faculty of Medicine, University of Reims Champagne-Ardenne, 51092 Reims, France.
Biochemistry Department, University Hospital of Reims, 51092 Reims, France.
Int J Mol Sci. 2022 Jan 5;23(1):574. doi: 10.3390/ijms23010574.
Carbamylation is a nonenzymatic post-translational modification resulting from the reaction between cyanate, a urea by-product, and proteins. In vivo and in vitro studies have demonstrated that carbamylation modifies protein structures and functions, triggering unfavourable molecular and cellular responses. An enhanced formation of carbamylation-derived products (CDPs) is observed in pathological contexts, especially during chronic kidney disease (CKD), because of increased blood urea. Significantly, studies have reported a positive correlation between serum CDPs and the evolutive state of renal failure. Further, serum concentrations of carbamylated proteins are characterized as strong predictors of mortality in end-stage renal disease patients. Over time, it is likely that these modified compounds become aggravating factors and promote long-term complications, including cardiovascular disorders and inflammation or immune system dysfunctions. These poor clinical outcomes have led researchers to consider strategies to prevent or slow down CDP formation. Even if growing evidence suggests the involvement of carbamylation in the pathophysiology of CKD, the real relevance of carbamylation is still unclear: is it a causal phenomenon, a metabolic consequence or just a biological feature? In this review, we discuss how carbamylation, a consequence of renal function decline, may become a causal phenomenon of kidney disease progression and how CDPs may be used as biomarkers.
氨甲酰化是一种非酶促的翻译后修饰，由尿素副产物氰酸盐与蛋白质之间的反应引起。体内和体外研究表明，氨甲酰化修饰了蛋白质的结构和功能，引发了不利的分子和细胞反应。在病理情况下，尤其是在慢性肾脏病（CKD）中，由于血液尿素增加，观察到氨甲酰化衍生产物（CDP）的形成增强。重要的是，研究报告了血清 CDP 与肾功能衰竭的进展状态之间存在正相关。此外，血清中氨甲酰化蛋白的浓度被认为是终末期肾病患者死亡率的强预测因子。随着时间的推移，这些修饰化合物可能成为加重因素，并促进长期并发症，包括心血管疾病和炎症或免疫系统功能障碍。这些不良的临床结果促使研究人员考虑预防或减缓 CDP 形成的策略。尽管越来越多的证据表明氨甲酰化参与了 CKD 的病理生理学，但氨甲酰化的真正相关性仍不清楚：它是一种因果现象、代谢后果还是仅仅是一种生物学特征？在这篇综述中，我们讨论了肾功能下降导致的氨甲酰化如何可能成为肾脏疾病进展的因果现象，以及 CDP 如何可用作生物标志物。
